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Pertuzumab in Combination with Trastuzumab and Docetaxel in Elderly Patients with HER2-Positive Metastatic Breast Cancer in the CLEOPATRA Study Miles D.

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Presentation on theme: "Pertuzumab in Combination with Trastuzumab and Docetaxel in Elderly Patients with HER2-Positive Metastatic Breast Cancer in the CLEOPATRA Study Miles D."— Presentation transcript:

1 Pertuzumab in Combination with Trastuzumab and Docetaxel in Elderly Patients with HER2-Positive Metastatic Breast Cancer in the CLEOPATRA Study Miles D et al. Proc SABCS 2012;Abstract P

2 Background Patients aged 65 years are underrepresented in trials of cancer treatments, thus limiting the availability of efficacy and safety data for new therapies in this population. The results from the Phase III CLEOPATRA trial evaluating the addition of pertuzumab versus placebo to trastuzumab/docetaxel for patients with HER2-positive metastatic breast cancer (mBC) (NEJM 2012;366:109): –Demonstrated a significant improvement in PFS with pertuzumab by independent review. –Led to the FDA approval of pertuzumab/trastuzumab/docetaxel as first-line therapy for HER2-positive mBC. Study objective: To compare the efficacy and safety of pertuzumab/trastuzumab/docetaxel according to age group for patients in the CLEOPATRA trial (<65 versus 65 years). Miles D et al. Proc SABCS 2012;Abstract P

3 Centrally confirmed HER2- positive locally recurrent, unresectable or metastatic BC (mBC) 1 hormonal regimen for mBC Prior (neo)adjuvant systemic Rx including trastuzumab allowed if followed by DFS 12 mo Baseline LVEF 50%; no CHF or LVEF <50% during or after prior trastuzumab Trastuzumab Docetaxel (6 cycles recommended) Trastuzumab Docetaxel (6 cycles recommended) Placebo Pertuzumab 1:1 N = 406 N = 402 R Primary endpoint: Independently assessed progression-free survival (PFS) CLEOPATRA Study Design Miles D et al. Proc SABCS 2012;Abstract P

4 Independently Assessed PFS (ITT Population) <65 years65 years PL/T/D (n = 339) Pert/T/D (n = 342) PL/T/D (n = 67) Pert/T/D (n = 60) Median PFS12.5 mo17.2 mo10.4 mo21.6 mo Hazard ratio % CI p-value< Miles D et al. Proc SABCS 2012;Abstract P PL = placebo; Pert = pertuzumab; T = trastuzumab; D = docetaxel

5 Exposure to Docetaxel Treatment <65 years65 years PL/T/D (n = 332) Pert/T/D (n = 346) PL/T/D (n = 65) Pert/T/D (n = 61) Median no. of cycles administered (range) 8.0 (1-41)8.0 (1-35)6.5 (1-26)6.0 (1-16) Median dose intensity, mg/m 2 /week Dose escalation, n (%)*53 (16.0)41 (11.8)8 (12.3)7 (11.5) Dose reduction, n (%) 72 (21.7)85 (24.6)17 (26.2)19 (31.1) Miles D et al. Proc SABCS 2012;Abstract P * Dose escalation to 100 mg/m 2 ; Dose reduction to <75 mg/m 2

6 Most Common Adverse Events: Overall (O) and After (A) Docetaxel Discontinuation All grades (O/A, %) <65 years65 years PL/T/DPert/T/DPL/T/D Pert/T/ D Diarrhea44.9/ / / /32.7 Neutropenia51.2/ / / /0 Fatigue36.1/ / / /16.3 Rash22.9/ / / /16.3 Asthenia29.2/ / / /4.1 Dysgeusia14.8/ / /027.9/4.1 Febrile neutropenia7.8/014.7/06.2/08.2/0 Overall, the proportion of patients 65 y receiving G-CSF was lower than that of patients <65 y. Miles D et al. Proc SABCS 2012;Abstract P

7 Most Common Adverse Events (Grade 3) <65 years65 years PL/T/D (n = 332) Pert/T/D (n = 346) PL/T/D (n = 65) Pert/T/D (n = 61) Neutropenia47.0%50.3%40.0%41.0% Leukopenia15.4%12.7%10.8%9.8% Febrile neutropenia7.8%14.7%6.2%8.2% Diarrhea4.8%6.6%6.2%14.8% Fatigue2.7%2.0%6.2%3.3% Peripheral neuropathy1.8%1.7%1.5%8.2% LVSD2.4%1.2%4.6%1.6% Asthenia1.2%2.9%3.1%0% Miles D et al. Proc SABCS 2012;Abstract P

8 Author Conclusions Treatment with Pert/T/D demonstrated a superior PFS by independent review in patients aged <65 years and 65 years compared with PL/T/D. In patients aged 65 years versus <65 years: –There were more dose reductions of docetaxel. –There was a lower median number of docetaxel cycles, which likely explains the lower incidence of neutropenia and febrile neutropenia and the less frequent use of G-CSF. The safety and efficacy data reported in the CLEOPATRA trial suggest that in patients with good ECOG PS, the combined use of Pert/T/D should not be limited by patient age. The PERUSE study will investigate the tolerability and efficacy of first-line Pert/T with one of a choice of taxanes in patients with HER2-positive mBC (NCT ). Miles D et al. Proc SABCS 2012;Abstract P

9 Investigator Commentary: Pertuzumab/Trastuzumab/Docetaxel for Elderly Patients with HER2-Positive mBC The results of the subset analysis of the CLEOPATRA trial based on age demonstrated that patients benefit from combination therapy with pertuzumab, trastuzumab and docetaxel irrespective of age. These results are consistent with what was found with anti-HER2 therapy in the adjuvant setting. It is a reminder that breast cancer should be managed based on the biology of the disease and the patients overall condition rather than age. Interview with Edith A Perez, MD, January 17, 2013 Anytime I see a survival advantage in any population of patients facing incurable metastatic breast cancer, I feel as if were making some progress in this area. To see the survival data from CLEOPATRA was exciting, and it was nice to see that the elderly population from CLEOPATRA not only derived a benefit but seemed to tolerate treatment well. No large outstanding safety signal was apparent. They required more dose reductions, but in general there were no more treatment-related deaths, and the responses appeared to be similar across the age groups. Interview with Kimberly L Blackwell, MD, January 8, 2013


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